Chapter 12 Cell surface ATP (P2y) purinoceptors trigger and modulate multiple calcium fluxes in skeletal muscle cells

Author(s):  
J. Häggblad ◽  
H. Eriksson ◽  
E. Heilbronn
2019 ◽  
Vol 317 (6) ◽  
pp. E957-E972
Author(s):  
Brent A. Fujimoto ◽  
Madison Young ◽  
Lamar Carter ◽  
Alina P. S. Pang ◽  
Michael J. Corley ◽  
...  

Skeletal muscle handles ~80–90% of the insulin-induced glucose uptake. In skeletal muscle, insulin binding to its cell surface receptor triggers redistribution of intracellular glucose transporter GLUT4 protein to the cell surface, enabling facilitated glucose uptake. In adipocytes, the eight-protein exocyst complex is an indispensable constituent in insulin-induced glucose uptake, as it is responsible for the targeted trafficking and plasma membrane-delivery of GLUT4. However, the role of the exocyst in skeletal muscle glucose uptake has never been investigated. Here we demonstrate that the exocyst is a necessary factor in insulin-induced glucose uptake in skeletal muscle cells as well. The exocyst complex colocalizes with GLUT4 storage vesicles in L6-GLUT4myc myoblasts at a basal state and associates with these vesicles during their translocation to the plasma membrane after insulin signaling. Moreover, we show that the exocyst inhibitor endosidin-2 and a heterozygous knockout of Exoc5 in skeletal myoblast cells both lead to impaired GLUT4 trafficking to the plasma membrane and hinder glucose uptake in response to an insulin stimulus. Our research is the first to establish that the exocyst complex regulates insulin-induced GLUT4 exocytosis and glucose metabolism in muscle cells. A deeper knowledge of the role of the exocyst complex in skeletal muscle tissue may help our understanding of insulin resistance in type 2 diabetes.


1971 ◽  
Vol 57 (2) ◽  
pp. 188-201 ◽  
Author(s):  
Ernest Page ◽  
Bert A. Mobley ◽  
Margaret Johnson ◽  
Judy E. Upshaw

Single skeletal muscle cells of Balanus contain 48 ± 1 mmoles magnesium/kg dry weight. Although 28Mg can be shown either to enter the cells or to be bound to the cell surface within less than 10 min, only 2.1 ± 0.3% of cellular or cell surface Mg exchanges with this isotope even after several hours. Glycerinated cells washed out in Tris buffer at low ionic strength retain ∼70% of the Mg present in intact cells. About 85% of this Mg is removed by extraction with KCl or NaCl at concentrations of K and Na which prevail in intact cells, as well as by pyrophosphate, Tris-ATP, or reduction of the ionized Mg concentration to 1 µM. Lowering the ionized Mg concentration to 0.1 µM does not further reduce the Mg content of glycerinated cells. The pH dependence of KCl-inextractable Mg suggests that more than one class of binding sites is involved. A significant fraction of the KCl-inextractable Mg bound to glycerinated cells fails to exchange with 28Mg even after long equilibration. It is suggested that this fraction may be actin-bound Mg incorporated into the thin filaments during the polymerization of actin.


2004 ◽  
Vol 59 (1) ◽  
pp. 89-101 ◽  
Author(s):  
Henrietta Szappanos ◽  
Julianna Cseri ◽  
Tamás Deli ◽  
László Kovács ◽  
László Csernoch

2006 ◽  
Vol 453 (4) ◽  
pp. 509-518 ◽  
Author(s):  
Gyula Péter Szigeti ◽  
Henrietta Szappanos ◽  
Tamás Deli ◽  
Julianna Cseri ◽  
László Kovács ◽  
...  

Endocrinology ◽  
2007 ◽  
Vol 148 (11) ◽  
pp. 5248-5257 ◽  
Author(s):  
Mònica Díaz ◽  
Costin N. Antonescu ◽  
Encarnación Capilla ◽  
Amira Klip ◽  
Josep V. Planas

In mammals, glucose transporter (GLUT)-4 plays an important role in glucose homeostasis mediating insulin action to increase glucose uptake in insulin-responsive tissues. In the basal state, GLUT4 is located in intracellular compartments and upon insulin stimulation is recruited to the plasma membrane, allowing glucose entry into the cell. Compared with mammals, fish are less efficient restoring plasma glucose after dietary or exogenous glucose administration. Recently our group cloned a GLUT4-homolog in skeletal muscle from brown trout (btGLUT4) that differs in protein motifs believed to be important for endocytosis and sorting of mammalian GLUT4. To study the traffic of btGLUT4, we generated a stable L6 muscle cell line overexpressing myc-tagged btGLUT4 (btGLUT4myc). Insulin stimulated btGLUT4myc recruitment to the cell surface, although to a lesser extent than rat-GLUT4myc, and enhanced glucose uptake. Interestingly, btGLUT4myc showed a higher steady-state level at the cell surface under basal conditions than rat-GLUT4myc due to a higher rate of recycling of btGLUT4myc and not to a slower endocytic rate, compared with rat-GLUT4myc. Furthermore, unlike rat-GLUT4myc, btGLUT4myc had a diffuse distribution throughout the cytoplasm of L6 myoblasts. In primary brown trout skeletal muscle cells, insulin also promoted the translocation of endogenous btGLUT4 to the plasma membrane and enhanced glucose transport. Moreover, btGLUT4 exhibited a diffuse intracellular localization in unstimulated trout myocytes. Our data suggest that btGLUT4 is subjected to a different intracellular traffic from rat-GLUT4 and may explain the relative glucose intolerance observed in fish.


2009 ◽  
Vol 297 (6) ◽  
pp. C1554-C1566 ◽  
Author(s):  
Boubacar Benziane ◽  
Marie Björnholm ◽  
Louise Lantier ◽  
Benoit Viollet ◽  
Juleen R. Zierath ◽  
...  

Muscle contraction and metabolic stress are potent activators of AMP-activated protein kinase (AMPK). AMPK restores energy balance by activating processes that produce energy while inhibiting those that consume energy. The role of AMPK in the regulation of active ion transport is unclear. Our aim was to determine the effect of the AMPK activator A-769662 on Na+-K+-ATPase function in skeletal muscle cells. Short-term incubation of differentiated rat L6 myotubes with 100 μM A-769662 increased AMPK and acetyl-CoA carboxylase (ACC) phosphorylation in parallel with decreased Na+-K+-ATPase α1-subunit abundance at the plasma membrane and ouabain-sensitive 86Rb+ uptake. Notably, the effect of A-769662 on Na+-K+-ATPase was similar in muscle cells that do not express AMPK α1- and α2-catalytic subunits. A-769662 directly inhibits the α1-isoform of the Na+-K+-ATPase, purified from rat and human kidney cells in vitro with IC50 57 μM and 220 μM, respectively. Inhibition of the Na+-K+-ATPase by 100 μM ouabain decreases sodium pump activity and cell surface abundance, similar to the effect of A-769662, without affecting AMPK and ACC phosphorylation. In conclusion, the AMPK activator A-769662 inhibits Na+-K+-ATPase activity and decreases the sodium pump cell surface abundance in L6 skeletal muscle cells. The effect of A-769662 on sodium pump is due to direct inhibition of the Na+-K+-ATPase activity, rather than AMPK activation. This AMPK-independent effect on Na+-K+-ATPase calls into question the use of A-769662 as a specific AMPK activator for metabolic studies.


Planta Medica ◽  
2016 ◽  
Vol 81 (S 01) ◽  
pp. S1-S381
Author(s):  
II Ezeigbo ◽  
C Wheeler-Jones ◽  
S Gibbons ◽  
ME Cleasby

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